Histidine and its derivatives increased rabbit muscle fructose 1, 6-bisphosphatase activity at neutral pH with positive cooperativity. In the presence of histidine and carnosine the optimum pH shifted from pH 8.0 to 7.4. The cooperative response of the enzyme to AMP and fructose 1, 6-bisphosphate was observed in the presence of the histidine derivatives.
Of a number of divalent cations tested, only Zn²⁺ was found to be an effective inhibitor of enzyme activity at low concentrations. The kinetic data suggested that Zn²⁺ acted as inhibitor as well as activator for the enzyme activity; a high affinity binding site was associated with K_l of approximately 0.5 μm Zn²⁺ and a catalytic site was associated with Km of approxi-mately 10 μm Zn²⁺. Rabbit muscle fructose 1, 6-bisphosphatase bound 4 equivalents of Zn²⁺/ mol, presumably I per subunit, in the absence of fructose 1, 6-bisphosphate. Two equivalents of Zn²⁺/mol bound to the enzyme were readily removed by dialysis or gel filtration in the absence of a chelating agent. The other two equivalents of Zn²⁺/mol were removed by his-tidine and histidine derivatives of naturally occurring chelators with concomitant increase in activity.